The overall objective of this project is to study the pathophysiology of glomerular injury, particularly in its early developmental stages, so as to discover the mechanisms of the adaptive changes in renal hemodynamics which occur during progressive glomerular injury and serve to maintain renal function. The effects of pure glomerular capillary obliteration on the renin-angiotensin system will be studied. Microspheres (14 diameter) will be injected into one kidney and the renin content and ultrastructure of the juxtaglomerular apparatus will be examined. Similar studies will be performed in rats with a left unilateral glomerulonephritis. Glomerular hemodynamics will be measured by direct micropuncture techniques in order to correlate changes in the renin system with changes in glomerular pressures and flows. Studies of the abnormalities in renal blood flow autoregulation in experimental glomerulonephritis will be continued. The role of the renin-angiotensin, prostaglandin and kinin systems will be determined by studying the influence of inhibitors of these systems on the autoregulatory changes occurring in animals with experimental glomerulonephritis. The adaptive changes in glomerular hemodynamics following induction of experimental glomerulonephritis and the role of prostaglandins, angiotensin and kinins will be studied utilizing selective agents. A study will be initiated relating the activity of the renin-angiotensin system to expansion of the extracellular fluid volume in hypertension in bilateral progressive experimental glomerulonephritis.